Ion channels



Ion channels are membrane proteins that catalyze the passive transport of ions through the cell membrane. Most ion channels are specific to an ion, like the sodium channels, or the chloride channels. Some, like the TRP channels, let through various cations. Another property of ion channels is that they can be either driven by voltage or concentration gradients, or they can be gated (by voltage, ligands, touch and other sensory signal). Potassium channels (KCh) are subdivided to voltage-gated KCh and calcium-dependent KCh. The latter are subdivided into high- (BK, LKCa), intermediate- and small-conductance KCh (human SK1, rat SK2, SKCa). MthK is a calcium-dependent potassium channel from Methanobacterium thermoautrophicum. MscL and MscS are large- and small-conductance mechanosensitive channels which protect bacteria from osmotic shock by allowing ions to flow across the cell membrane. Voltage-Dependent Calcium Channels (VDCC) allow Ca++ to enter the cell resulting in muscle contraction, neuron excitation or hormone release. VDCC are composed of several subunits and are named as a Cav gene product. Finally, ion channels are the fastest of all membrane transporters, with 106 to 108 transported units per second versus 102 to 104 molecules per second for porters/carriers, or 100 to 103 for ATP-driven pumps. The images at the left and at the right correspond to one representative ion channel structure, i.e. the crystal structure of voltage-dependent potassium channel from Rattus norvegicus (1qrq). M2 Proton Channel gives details on proton channels and Chloride Ion Channel on chloride channels.

Classification
TCDB, the most sophisticated classification of transport proteins to date, classify ion channels as a heterogenous subset of all &alpha;-type channels, whose singular property is to consist mainly of &alpha;-helices that span the membrane. They are distinct in this from the beta-barrel porins and the pore-forming toxins, as well as from non-ribosomally synthesized channels like gramicidin, polyglutamine or digitoxin. All these proteins are passive transport proteins.

Additional Resources
For additional information, see: Membrane Channels & Pumps For additional information, see: Hypertension & Congestive Heart Failure

Available 3D structures
Ion channels translate ionic fluxes across cell membrane into electrical impulses. MscL and MscS are large- and small-conductance mechanosensitive channels which protect bacteria from osmotic shock by allowing ions to flow across the cell membrane. Voltage-Dependent Calcium Channels (VDCC) allow Ca to enter the cell resulting in muscle contraction, neuron excitation or hormone release. VDCC are composed of several subunits and are named as a Cav gene product. The human annexin V molecule serves as a calcium channel. There are also Voltage-Dependent Anion Channels (VDAC). Chloride ion channels (ClCh) are involved in maintaining pH, volume homeostasis and more. Ligand-Gated Ion Channels (LGIC) open or close when binding a ligand like a neurotransmitter. The Cyclic Nucleotide-Gated channel (CNGC) conduct cations upon binding of cAMP or cGMP. The Acid-Sensitive channels (ASC) conduct cations upon binding of acid. The glycerol facilitator (GlpF) is a protein channel which transports glycerol across the cell membrane of E. coli. Other ion channel proteins are the aquaporins, gramicidin, antiamoebin, trichotoxin, peptaibol and the glutamate receptor.

Potassium channel
See: Potassium Channels

Calcium channel
3bxx – rCav2.1 alpha 1A subunit+calmodulin

3bxl - rCav2.3 alpha 1E subunit+calmodulin

2f3y, 2f3z, 2be6 – hCav1.2 alpha 1C subunit+calmodulin

1t0h – rVDCC beta 2A subunit

1t0j – rVDCC beta 2A+alpha 1C

1vyt - rVDCC beta 3+alpha 1C

1vyu – rVDCC beta 3

1vyv - rVDCC beta 4

1t3l - raVDCC beta 2+alpha 1S – rabbit

1t3s - raVDCC beta 2

2d46 – hVDCC beta 4a – NMR

3dve, 3dvj, 3dvk, 3dvm, 3g43 - rCav2.2 alpha 1B subunit+hCalmodulin

3oxq - hCav2.1 alpha 1C subunit IQ domain+hCalmodulin

2vay - hCav1.1 alpha 1S subunit IQ domain+hCalmodulin

1hvd, 1hve, 1hvf, 1hvg – hAnnexin V (mutant)

Sodium channel
1byy - rNaCh IIA inactivation fragment

2kav, 2kbi - hNaCh IIA C-terminal EF-hand domain - NMR

NH4+ channel
2nmr, 2nop, 2now, 2npc, 2npd, 2npe, 2npj, 2npg, 2npk, 1u77, 1u7c, 1u7g, 1xqe, 1xqf – EcAmCh – Escherichia coli

2b2h, 2b2i, 2b2j, 2b2f – AmCh – Archaeglobus fulgidus

3b9w, 3b9y, 3bhs – AmCh – Nitrosomonas europaea

MscL and MscS
3hzq – MscL – Staphylococcus aureus

2oar – MscL – Mycobacterium tuberculosis

2oau, 2vv5 - EcMscS

Chloride channel
1rk4 - hClCh protein 1

3o3t, 3p8w, 3p90, 1k0o, 3qr6 - hClCh protein 1 (mutant)

2per, 2r4v, 2r5g - hClCh protein 2

3kjy, 3fy7 - hClCh protein 3 residues 1-230

2ahe, 2d2z – hClCh protein 4

Anion Channel
2jk4 – hVDAC

Ligand-gated ion channel
2vl0 – LGIC – Erwinia chrysanthemi

2xq3, 2xq4, 2xq5, 2xq6, 2xq7, 2xqa, 2xq8 – GvLGIC+inhibitor – Gloeobacter violaceus

3eam, 3ehz – GvLGIC

3igq – GvLGIC N-terminal

2xq9 – GvLGIC (mutant)+inhibitor

3lsv – GvLGIC (mutant)

Cyclic Nucleotide-Gated channel
3etq, 3ffq – mCNGC C-terminal

1q3e, 1q43, 1q5o - mCNGC 2 fragment + nucleotide

2q0a - mCNGC 2 C-terminal (mutant)

3bpz - mCNGC 2 ligand-binding domain

2zd9, 3beh - MlCNGC

2ptm - CNGC C-terminal - Strongylocentratus purpuratus

Acid sensitive ion channel
3hgc, 3ij4, 2qts – ASC – chicken

ATP-Gated channel (AGC)
3h9v, 3i5d – AGC – Zebra fish

Proton channel
2kih, 2kwx – IVproton channel – Influenza virus

2rtf - IVproton channel + inhibitor - NMR

3c9j - IVproton channel transmembrane domain + inhibitor

3bkd - IVproton channel transmembrane domain

1nyj, 1mp6 - IVproton channel transmembrane domain - NMR

2kj1, 2l0j - IVproton channel – NMR

Voltage-gated hydrogen channel (VGHC)
3a2a – hVGHC C-terminal - NMR

Nicotinic acetylcholine receptor
1oed, 2bg9 - AChR - Torpeco marmorata - EM

2k58 - AChR β2 subunit 1st transmembrane domain - NMR

2k59 - AChR β2 subunit - NMR

Tryptophan channel
2rfa - mTrpCh ankyrin repeat domain

3e7k - rTrpCh tetramerization domain

Glycerol facilitator
1lda, 1ldi - EcGlpF

1fx8 - EcGlpF + glycerol

1ldf - EcGlpF (mutant)

Weblinks

 * The TCDB database
 * TCDB: 1.A α-Type channels
 * TCDB: Transport proteins with PDB structures